Phorbol myristate acetate-induced proliferation of an IL-2-dependent T-cell line: action of PMA is independent of IL-2 and cannot be mimicked by diacylglycerols

Phorbol myristate acetate (PMA) at concentrations of 2 X 10(-10) to 2 X 10(-7) M was able to sustain proliferation of the interleukin 2 (IL-2)-dependent murine T-cell line CTLL-K. This line, which died within 24 hr without exogenously added IL-2, survived for at least 96 hr and completed two to three cycles of replication in the presence of an optimal dose of PMA. PMA did not increase proliferation induced by saturating amounts of IL-2, but it mimicked IL-2 activity when no IL-2 or only suboptimal doses of IL-2 were present. This effect was completely independent of any residual IL-2 activity and was not mediated by the endogenous production of IL-2. The finding that stimulation of CTLL-K cells with 1-oleoyl-2-acetyl-glycerol or 1,2-dioctanoyl-glycerol rather than with PMA was not sufficient to induce any proliferation suggests that diacylglycerols and phorbol esters have qualitatively different effects on protein kinase C activity. Falsely positive results could occur when IL-2-dependent T-cell lines were used as indicator cells for IL-2, since evidence is presented that PMA-responsive cells could emerge spontaneously from T-cell clones that originally were not responsive or only weakly influenced by PMA.